Rheumatoid arthritis causes significant pain and disability because more than half of the patients suffering therewith have synovial inflammation of the knee joint. Treatment is directed towards controlling the inflammation. Aspirin, non-steroidal anti-inflammatory agents and intra-articular administration of corticosteroids are treatments most commonly used.
In cases where this treatment is unsuccessful, surgical removal of the inflamed synovial membrane has been shown to give relief for 2 to 5 years. However, this method has the major disadvantage of prolonged hospitalisation, especially for older patients.
In Europe and Australia, radiation synovectomy is used as an alternative to surgery. This treatment consists of the intra-articular injection of a beta emitting radionuclide in either a colloidal or particulate form. The radiation dose destroys the inflamed tissue. Yttrium-90 and gold-198 are the most frequently used radionuclides. Very often these radionuclides have been used as colloidal suspensions, for example as a colloid of yttrium silicate.
Although radiation synovectomy has been shown to be effective for the treatment of synovitis of joints, it has not obtained widespread acceptance because of the signicant leakages that occur from the joint with these preparations. The leakage (related to particle size) when combined with the relatively long half-life of approximately 2.7 days of each results in significant integrated radiation doses to other organs, such as the lymph nodes, liver and kidneys. The lymph nodes for example can receive a dose of 9,100 rads as a result of leakage after a 185 MBq (megaBecquerals) injection of yttrium-90 silicate colloid to the knee joint.
Larger particles (macroaggregates) have been used in an effort to reduce leakage. When the radionuclide has been used in the form of the hydroxide, ferric hydroxide has always been co-precipitated, as for example with yttrium hydroxide (Y-FHMA). The ferric hydroxide has traditionally acted as a useful identifier providing a visible suspension.
Research in the USA has shown that the problem of leakage of radioactivity can also be significantly reduced by using the much shorter half-life radionuclide, dysprosium-165 (half-life 139 minutes). The preparation (Dy-FHMA) like Y-FHMA, consists of a mixture of ferric hydroxide and dysprosium hydroxide macroaggregates suspended in saline.
Surprisingly the inventors have found that a further improvement to this technique is the elimination altogether of the ferric hydroxide. Ferric hydroxide has been found to be unnecessary for the efficacy of either Dy-165 or Y-90 and in fact there is evidence to suggest that ferric ions actually induce further inflammation in arthritic joints. In addition there is the risk of a patient undergoing what is termed "iron-shock".
Whilst a suspension comprising dysprosium-165 hydroxide macroaggregates free of ferric hydroxide (Dy-HMA) is the preferred agent for patients that are less than 10 hours transport time from a reactor, a suspension of yttrium-90 hydroxide macroaggregates (Y-HMA) must still be used for patients more than 10 hours from the reactor, since the amounts of dysprosium that would need to be injected to obtain the required dose of 11 GBq, would be toxic.